The Principal Investigator has isolated from porcine deodenum a new hormone-like peptide called chymodenin, which exhibits a unique biological activity: the selective and perhaps exclusive enhancement of chymotrypsinogen secretion relative to other digestive enzymes by the pancreas. Chymodenin produces a dramatic increase in chymotrypsinogen secretion by the pancreas, which is accompanied by a modest increase in protein output, and no increase in the basal rate of lipase secretion. Chymodenin's effects are unique, in that other stimulants of pancreatic secretion cause a massive, non-selective increase in protein output by the pancreas. The broad objectives of this proposal are to study chymodenin's hormonal status-is it a new gastrointestinal hormone? We are approaching completion of the amino acid sequence, and will continue chemical characterization of the molecule. We plan to study the two disulfide bonds and their importance for physiological activity; the possibility of active fragments of chymodenin and the significance of the pentapeptide sequence shared by chymodenin and Gastric Inhibitory Peptide (GIP) will be explored. The radioimmunoassay we have developed will be used together with bioassays to study serum levels of chymodenin, the stimuli eliciting release of chymodenin, and the dose-response relationships of its activity in vivo.